The objective of this study is to elucidate the basic mechanisms involved in the regultion of erthropoiesis and to apply this knowledge to human erythropoietic diseases. Erythropoietin appears to have a primary effect on the cytoplasmic membrane of marrow cells to produce an active marrow cytoplasmic factor (MCF) that stimulates nuclear RNA and DNA synthesis. The relationship of the hormone's stimulation of cyclic GMP to its stimulation of the MCF and RNA or DNA synthesis will be investigated. The polycythemia produced by the Fried Virus (FVP) will also be studied. FVP markedly increases erythropoiesis in mice by a mechanism that does not require erythropoietin. The virus will be injected into animals and then the spleen cells will be cultured. Production of lymphatic leukemia virus and spleen focus-forming virus by the infected spleen cell in vitro will be determined. The effect of the virus on RNA, DNA, and protein synthesis by mouse spleen cell in vitro will be studied to determine if its mechanism of action is similar to erythropoietin. Metabolic inhibitors will be employed to determine the primary effect of FVP. An attempt will be made to infect erythroid cells with the virus in vitro and study the effect of the virus on hemoglobin synthesis. The methods developed in these investigations will be applied to the study of polycythemia vera. The amount of MCF in polycythemia vera marrows will be measured and compared to the amount in secondary polycythemia marrows. It is conceivable that the increased erythropoiesis in this disease is due to an abnormal control of the MCF.